Elucidation of gene expression patterns in the brain after spinal cord injury

Abstract

Spinal cord injury (SCI) is a devastating neurological disease. The pathophysiological mechanisms of SCI have been reported to be relevant to central nervous system injury such as brain injury. Recent studies have shown that SCI causes brain inflammation, progression of nerve cell loss as well as loss of brain functions. In this study, gene expression of the brain after SCI was elucidated using transcriptome analysis to characterize the temporal changes in global gene expression patterns in a SCI mouse model. Subjects were randomly classified into three groups: sham control, acute (3 hour-post-injury) and subacute (2 week-post-injury) groups. We sought to confirm the differentially expressed genes (DEGs) between post-injured groups and sham control groups. Therefore, we performed transcriptome analysis to investigate the enriched pathways associated with pathophysiology of the brain after SCI using Database of Annotation Visualization and Integrated Discovery (DAVID), which yielded Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Following enriched pathways were found in brain: oxidative phosphorylation pathway, inflammatory response pathways—cytokine-cytokine receptor interaction, chemokine signaling pathway—, ER stress related pathways: antigen processing and presentation, and MAPK signaling pathway. Oxidative phosphorylation was identified at acute phase, while inflammation response and ER stress related pathway were identified at subacute phase. Our study provided gene expression patterns in brain after SCI in pathophysiological processes. In brain after SCI, mitochondria dysfunction occurred at acute phase, sequentially inflammatory response and ER stress aroused at subacute phase. Finally, these stress environments led to activation of MAPK signaling pathway at subacute phase compared to acute phase. These pathophysiological mechanisms already have been reported in SCI. Our results emphasized that SCI is closely associated with brain injuries. Hence, these mechanisms may provide not only a link between SCI and brain injury, but also valuable reference data for understanding gene expression patterns at acute phase and subacute phase.